Selective CXCR4 antagonism by Tat:: Implications for in vivo expansion of coreceptor use by HIV-1
Selective CXCR4 antagonism by Tat:: Implications for in vivo expansion of coreceptor use by HIV-1
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DOI：
10.1073/pnas.97.21.11466
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发表时间：
2000-10-10
影响因子：
11.1
通讯作者：
Jeang, KT
中科院分区：
文献类型：
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作者：
Xiao, H;Neuveut, C;Jeang, KT
趋化因子和趋化因子受体在HIV-1的感染和嗜性中起重要作用，CCR 5是HIV-1的主要嗜巨噬细胞辅助受体，而CXC趋化因子受体4（CXCR 4）对嗜T细胞病毒起对应的功能。一个突出的生物学之谜是为什么只有R5-HIV-1最初在暴露于R5和X4病毒的新血清转化者中被检测到。事实上，X4病毒出现在少数患者中，并且仅出现在疾病的晚期，这表明可能存在针对HIV-1-CXCR 4相互作用的早期阴性选择。在这里，我们报告说，HIV-1达特蛋白，这是从病毒感染的细胞分泌，是CXCR 4特异性拮抗剂。可溶性达特选择性抑制X4病毒进入外周血单个核细胞（PBMC）并复制，但不抑制R5病毒。我们提出分泌的达特的一个功能性结果是选择抗X4病毒，从而影响HIV-1疾病的早期体内过程。
Chemokines and chemokine receptors play important roles in HIV-1 infection and tropism, CCR5 is the major macrophage-tropic: coreceptor for HIV-1 whereas CXC chemokine receptor 4 (CXCR4) serves the counterpart function for T cell-tropic viruses. An outstanding biological mystery is why only R5-HIV-1 is initially detected in new seroconvertors who are exposed to R5 and X4 viruses. Indeed, X4 virus emerges in a minority of patients and only in the late stage of disease, suggesting that early negative selection against HIV-1-CXCR4 interaction may exist. Here, we report that the HIV-1 Tat protein, which is secreted from virus-infected cells, is a CXCR4-specific antagonist. Soluble Tat selectively inhibited the entry and replication of X4, but not R5, virus in peripheral blood mononuclear cells (PBMCs). We propose that one functional consequence of secreted Tat is to select against X4 viruses, thereby influencing the early in vivo course of HIV-1 disease.